With an increasing emphasis on small-animal disease models, radiological imaging of small animals has many of the needs that have been refined for human radiology. However, the present inventors have found that X-ray energies and image resolution that have been employed for human radiology are not easily extrapolated to small animals. For example, for quality analysis, the present inventors have found that small animal bones may require about ten times the resolution of that useful for human bones. Further, the present inventors have found that small animal bones require use of a lower range of X-ray energies due to the markedly different X-ray absorption characteristics of such small bones. Some of the best examples of film radiography may have approached the necessary spatial resolution to delineate fine bone features of small animals. The best efforts made using film radiography are known to the present inventors to present difficulties achieving adequate precision (film is insufficiently reproducible) and ergonomics (multiple films and processing time). While digital imaging is ergonomic, sufficient spatial resolution has not been clearly demonstrated. It would be desirable to have an apparatus and method capable of using high resolution phosphor screens and low energy X-rays to provide digital images sufficient for easy and efficient measurement of the long bone density of small animals.
Reference is made to commonly assigned U.S. Pat. No. 5,830,629 of Vizard et al; U.S. Pat. No. 6,346,707 of Vizard et al; and U.S. Pat. No. 6,444,988 of Vizard, each of which is incorporated by reference into this specification. Collectively, these patents disclose the essential features of a radiographic phosphor screen that may be used in the X-ray imaging system that the present inventors have found to be useful in the practice of the present invention. The technology disclosed in these patents has been used in the family of Kodak Imaging System 4000 products currently marketed by Carestream Health, Inc. These products, formerly marketed by Eastman Kodak Company, for the most part are capable of imaging objects using several imaging modalities, including X-ray, radio-isotopic, bright field and dark field (fluorescence and luminescence) modes. The IS4000 family comprises five distinct products now sold by Carestream Health, Inc. that are suitable for use in accordance with the present invention: (1) the “KODAK In-Vivo Imaging System FX”; (2) the “KODAK In-Vivo Imaging System FX Pro” which is similar to the “KODAK In-Vivo Imaging System FX” but also has a precision robotic operation (PRO); (3) the “KODAK In-Vivo Multispectral System FX” which is similar to the “KODAK In-Vivo Imaging System FX Pro” but also has more excitation filters and additional software; (4) the “KODAK Digital X-ray Specimen 4000 System;” and (5) the “KODAK Digital X-ray Specimen 4000 Pro System.” The last two products are similar to the “KODAK In-Vivo Imaging System FX” and the “KODAK In-Vivo Imaging System FX Pro”, respectively, except they do not have a fluorescent imaging capability.
FIG. 1 shows a diagrammatic view of an electronic imaging apparatus; and FIG. 2 shows an elevation view of a phosphor plate or screen as disclosed in previously mentioned U.S. Pat. No. 6,346,707. Such an apparatus and screen are useful in the practice of the present invention. Electronic imaging system 10 includes a housing 12, an imaging assemblage 14 (including a phosphor plate or screen), a digital camera 16 and a light transmission 18 including a mirror 20 in a mirror housing 21. Mirror 20 is supported on a foam pad 22 and adjustments 23 may be provided for adjusting the position of mirror 20. Housing 21 includes a retainer 24. Image transmission system 18 further includes a diopter 25 and a zoom lens 26. Camera 16 is connected to a computer, not shown, having a display 40 where captured images may be viewed.
An ionizing radiation source 30 may be used to produce an ionizing radiation image which is converted by imaging assemblage 14 into a light image. An auto-radiographic source 30 (such as a small animal or tissue sample treated with a suitable radioisotope) may be provided in contact with assemblage 14. Alternatively, source 30 can be located a distance from assemblage 14 and be a source of X-radiation, electron radiation, or ultraviolet radiation. In the latter case, an object to be imaged is placed on a support stage, not shown, between the source and assemblage 14 and a radiation image is projected to assemblage 14. For example, as also shown in FIG. 1, the ionizing radiation source may be an X-ray source 30A comprising an X-ray generator with a micro-focus aperture that produces a controlled emission characterized by a spot size. As shown schematically in FIG. 1, an assemblage of X-ray filters 30B (qualified Aluminum sheets of differing thickness) may be placed in the X-ray beam path to act as high pass filters, thus enabling user control of the mean energy of the X-rays that irradiate an object to be imaged. FIG. 3 shows a graphical representation of an energy spectrum of emitted X-rays in the apparatus of FIGS. 1 and 2 when used in accordance with the present invention. The spectrum is a histogram of X-ray energies (Kev, Kilo electron volts) emitted from an X-ray head with no added filtration other than a 0.005″ Be window. The spectrum is from an X-ray tube operating at 30 Kvp. The peaks labeled “W” correspond to the expected from the tungsten target.
As shown in FIG. 2, imaging assemblage 14 includes a thin protective layer 31, a phosphor layer 32, a transparent support layer 34 with a boundary layer of air (not shown) between support 34 and phosphor 32. The phosphor layer 32 contains a prompt phosphor capable of absorbing an ionizing radiation image to produce a corresponding light image for capture by camera 16. Assemblage 14 is removable from the optical path shown in FIG. 1 in order to accommodate other optical modes imaging. The phosphor layer or screen may take any convenient form as disclosed in the three Vizard patents previously mentioned.
U.S. Patent Application Publication No. 2006/0222223 of Bi et al. discloses using a mammography device to obtain an image of a human finger bone and to analyze the bone's condition with computer-aided diagnosis (CAD) software. Bi does not discuss the use of the mammography device for determining the bone density in small animals such as rats and mice.
U.S. Pat. No. 7,054,409 of Ross et al. discusses how computed tomography (CT) detectors may not provide sufficient resolution to accurately resolve structures on the order of 0.5 to 1.5 mm and how the lack of resolution may be problematic in applications where greater resolution is desired, such as inner ear imaging, cardiac and vascular imaging, small animal imaging, and oncological screening. Ross discloses a method and device for imaging small bones such as those in small animals but does not discuss the use of such as device to determine the density of the bones that were imaged.
U.S. Pat. No. 6,320,931 of Arnold discloses a low cost X-ray bone densitometer capable of measuring bone density in the human body. The method described requires the use of a calibration phantom such as calcium hydroxyapatite in a solid tissue equivalent matrix to form the reference calibration phantom, which is positioned adjacent to the fingers for simultaneous calibration on each exam.
U.S. Pat. No. 6,990,222 of Arnold uses a number of computed tomography (CT) calibrations and beam hardening corrections based on idealized phantoms, which are often circular in shape and composed of water, plastics, or other synthetic materials. U.S. Pat. No. 4,721,112 of Hirano et al. discusses a method for bone evaluation carried out by determining a bone density distribution, from the modified bone pattern, by setting a bone model having an elliptic bone cross-sectional external shape, a zonate bone cortex, and a bone density decreasing portion in the inside of the bone cortex. The bone density distribution in each portion is classified, by color, based on the density values, and the X-ray image or photon absorptiometry image is converted to the image of the bone density distribution.
In an article entitled “Computerized methods for X-ray-based small bone densitometry” published in Computer Methods and Programs in Biomedicine (2004), 73, 35-42, Haidekker et al. describe a method for measuring bone density of small animals in which photographic film is used to capture an X-ray image. The film then is scanned to produce a digitized image that is analyzed to produce density measurements. The authors describe a considerable effort devoted to calibrating films using images considered acceptable. There is no recognition of the significance of low X-ray energy levels and high resolution phosphor plates to provide useful X-ray images in the manner disclosed by the present inventors.